Meropenem Population Pharmacokinetics and Dosing Regimen Optimization in Critically Ill Children Receiving Continuous Renal Replacement Therapy.
Journal
Clinical pharmacokinetics
ISSN: 1179-1926
Titre abrégé: Clin Pharmacokinet
Pays: Switzerland
ID NLM: 7606849
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
accepted:
06
09
2022
pubmed:
18
10
2022
medline:
16
11
2022
entrez:
17
10
2022
Statut:
ppublish
Résumé
We aimed to develop a meropenem population pharmacokinetic model in critically ill children receiving continuous renal replacement therapy and simulate dosing regimens to optimize patient exposure. Meropenem plasma concentration was quantified by high-performance liquid chromatography. Meropenem pharmacokinetics was investigated using a non-linear mixed-effect modeling approach. Monte Carlo simulations were performed to compute the optimal scheme of administration, according to the target of a 100% inter-dose interval time in which concentration is one to four times above the minimum inhibitory concentration (100% fT>1-4×MIC). A total of 27 patients with a median age of 4 [interquartile range 0-11] years, a median body weight of 16 [range 7-35] kg receiving continuous renal replacement therapy were included. Concentration-time courses were best described by a one-compartment model with first-order elimination. Body weight (BW) produced significant effects on volume of distribution (V) and BW and continuous renal replacement therapy effluent flow rate (Q Meropenem exposure in critically ill children receiving continuous renal replacement therapy needs dosing adjustments to the minimum inhibitory concentration that take into account body weight and the continuous renal replacement therapy effluent flow rate.
Sections du résumé
BACKGROUND AND OBJECTIVE
We aimed to develop a meropenem population pharmacokinetic model in critically ill children receiving continuous renal replacement therapy and simulate dosing regimens to optimize patient exposure.
METHODS
Meropenem plasma concentration was quantified by high-performance liquid chromatography. Meropenem pharmacokinetics was investigated using a non-linear mixed-effect modeling approach. Monte Carlo simulations were performed to compute the optimal scheme of administration, according to the target of a 100% inter-dose interval time in which concentration is one to four times above the minimum inhibitory concentration (100% fT>1-4×MIC).
RESULTS
A total of 27 patients with a median age of 4 [interquartile range 0-11] years, a median body weight of 16 [range 7-35] kg receiving continuous renal replacement therapy were included. Concentration-time courses were best described by a one-compartment model with first-order elimination. Body weight (BW) produced significant effects on volume of distribution (V) and BW and continuous renal replacement therapy effluent flow rate (Q
CONCLUSIONS
Meropenem exposure in critically ill children receiving continuous renal replacement therapy needs dosing adjustments to the minimum inhibitory concentration that take into account body weight and the continuous renal replacement therapy effluent flow rate.
Identifiants
pubmed: 36251162
doi: 10.1007/s40262-022-01179-2
pii: 10.1007/s40262-022-01179-2
doi:
Substances chimiques
Meropenem
FV9J3JU8B1
Anti-Bacterial Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1609-1621Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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